A multi-dimensional omics framework identifies GPR35 as a driver of M2 macrophage activation and poor prognosis in colorectal cancer - PubMed
5 days ago
- #GPR35
- #Tumor Microenvironment
- #Colorectal Cancer
- Colorectal cancer (CRC) is a leading cause of global cancer mortality, with outcomes influenced by the tumor microenvironment (TME).
- A multi-dimensional omics framework identified GPR35 as a key driver of M2 macrophage activation and poor prognosis in CRC.
- Single-cell RNA-seq data integration revealed nine intratumoral heterogeneity meta-programs (MPs), with MP8 linked to M2 macrophage activation.
- GPR35 was identified as a master regulator within the MP8-associated gene network through high-dimensional WGCNA.
- Clinical analysis across four independent cohorts confirmed GPR35 as a significant predictor of poor prognosis in CRC.
- GPR35 knockdown impaired CRC cell proliferation, migration, and invasion in vitro.
- High GPR35 expression correlated with an immune-excluded microenvironment, reduced cytotoxic T cell and NK cell recruitment, and elevated immune checkpoint expression.
- GPR35 expression negatively correlated with immunotherapy response signatures and was associated with aggressive mutational landscapes.
- GPR35 is proposed as a novel therapeutic target to enhance immune checkpoint blockade efficacy in 'cold' CRC tumors.